Recent molecular pharmacological studies have identified a new receptor class which resembles alpha 2 adrenoceptors but because of subtle differences has been named by a variety of descriptors including imidazole receptors. These receptors have been implicated as being important in controlling hypertension. However, studies to further define the physiologic importance of this receptor class have been limited by the lack of information available on the molecular structure of the endogenous ligand(s) and the receptors. During Phase I, we propose to be the first group to isolate, purify and characterize the putative endogenous ligand(s) for imidazole receptors. We propose to use the structures of the endogenous ligand(s) as leads for the design and synthesis of new therapeutic agents to interact with imidazole receptors.